Genetic Variants in MMP9 and TCF2 Contribute to Susceptibility to Lung Cancer

Objective: The Wnt signaling pathway is crucial for pulmonary development and differentiation; dysregulation of the Wnt signaling pathway may impair lung function. Indeed, single nucleotide polymorphisms (SNPs) of Wnt pathway-related genes have been suggested as risk factors for certain types of cancers. In this study, we aimed to evaluate the influence of SNPs in Wnt-related genes (TCF2, MMP9) on susceptibility to lung cancer. Methods: Polymorphisms of TCF2 rs4430796, MMP9 rs2250889, and MMP9 rs17576 were studied in Han Chinese subjects, including 135 patients with lung cancer and 176 controls, using the Sequenom MassARRAY platform. The association of genotypes with susceptibility to lung cancer was analyzed using odds ratio (OR), with 95% confidence interval (95% CI) and chi(2). Results: The three SNPs (rs4430796, rs2250889, and rs17576) were found to be significantly associated with an increased risk of lung cancer. The AA genotype and AG+AA genotype of rs4430796 showed a significantly increased susceptibility to lung cancer compared with the GG genotype (adjusted OR=6.03, 95% CI: 1.30-28.09, P=0.022; 5.55, 95% CI: 1.20-25.58, P=0.028). Compared with the rs17576 GG genotype, the AG and AG+AA genotypes were also associated with a significant risk (adjusted OR=2.65, 95% CI: 1.60-4.37, P=0.001; 2.57, 95% CI: 1.59-4.19, P <= 0.001) whereas the rs2250889 CG and CG+GG genotypes had 2.97-fold (95% CI: 1.81-4.85; P <= 0.001) and 2.80-fold increased associations with lung cancer (95% CI: 1.73-4.54; P <= 0.001), respectively, compared with the rs2250889 CC genotype. Furthermore, the association of rs4430796 with lung cancer became insignificant (P>0.05) after adjusting for gender and rs2250889. Conclusion: The three SNPs may play a role in the predisposition of members of the Han Chinese population to lung cancer.